Study: Genetic Risk for ADHD Linked to Alzheimer’s Disease, Cognitive Decline
A genetic predisposition for ADHD is associated with late-onset cognitive decline, memory impairment, and neurodegenerative conditions, according to a limited longitudinal study of older adults. More research is needed to support this newfound genetic correlation.
December 22, 2022
Older adults with a genetic risk for ADHD may be more susceptible to cognitive decline and Alzheimer’s Disease (AD).1 These results, published recently in Molecular Psychiatry, shed light on ADHD-related vulnerability to cognitive impairments as people age.
The ADHD polygenic risk score (ADHD-PRS) “represents the combined genetic liability for the disorder” and “is highly associated with ADHD diagnosis and related traits in independent clinical and population samples.” Researchers found that a higher ADHD-PRS was associated with greater decline of cognitive performance and memory impairment over time, and persistent executive function deficits compared to participant baselines. Study participants included adults aged 55 to 90 without a clinical diagnosis for ADHD or cognitive impairments.
The Preclinical Alzheimer’s Cognitive Composite (PACC) detects early signs of decline in cognitive function and was adapted to the current study. An association between higher ADHD-PRS and decreased PACC scores over time was observed in amyloid-β- (Aβ) positive individuals (35.4% of participants) using PET scans. The same was not found for Aβ-negative individuals, indicating an interaction between ADHD-PRS and brain Aβ deposition on cognitive decline.
“It is well established that around 30% of CU individuals older than 55 years of age present brain Aβ pathology and that a large portion of these individuals remain cognitively intact during their lives,” the researchers wrote. “This supports that the association between Aβ accumulation and cognitive deterioration depends on patients’ intrinsic resilience and susceptibility mechanisms. Together, the results above indicate that the genetic liability to ADHD plays a role in increasing the susceptibility to the harmful effects oft in the human brain.”
In Aβ-positive individuals, higher ADHD-PRS was also associated with forthcoming tau pathology and brain atrophy in frontal and parietal brain regions. Tau pathology was measured based on cerebrospinal fluid (CSF) concentrations.
Researchers used data from the Alzheimer’s Disease Neuroimaging Initiative. A total of 212 participants (116 females, 96 males) were included and identified as cognitively unimpaired (CU), or without memory impairments, at the onset. Participants completed a baseline assessment and were observed routinely after that for 6 years.
This is the first study to find a genetic correlation between ADHD and AD, so supporting research is needed. A detailed clinical assessment for ADHD diagnosis was not included and would benefit future research. In addition, all participants self-reported as white. Neuropsychiatric conditions, including depression and bipolar disorder, were excluded. These limitations should be considered to include participants that better represent the general ADHD population and diverse groups.
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1Leffa, D.T., Ferrari-Souza, J.P., Bellaver, B. et al. Genetic risk for attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer’s disease pathophysiology in cognitively unimpaired older adults. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01867-2
